Many recent studies have demonstrated the efficacy of interstitial ablative approaches for the treatment of hepatic tumors, including chemical ablation, cryoablation, and thermal ablation using energy sources like RF, laser, microwave, or focused ultrasound. Despite these promising results, current systems remain highly dependent on operator skill, and cannot treat many tumors because there is little control of the size and shape of the zone of necrosis, and no control over ablator trajectory within tissue. Remedying this problem requires advances in end-effector design, precise steering of the ablator device to the desired target location, and real- time monitoring of the zone of necrosis to ensure complete treatment. Intra-procedure ultrasound imaging provides perhaps the optimal and most readily available method for targeting, but simultaneous manual handling of the B-mode ultrasound (US) probe and the ablator device is a challenging task that is prone to significant errors in the hands of even the most experienced physicians. Tissue deformation and target motion make it extremely difficult to place the ablator device precisely into the target. Irregularly shaped target volumes typically require multiple insertions and several overlapping thermal lesions, which are even more challenging to accomplish in a precise and timely manner without causing excessive damage to surrounding normal tissues. In answer to these problems, we propose to develop an innovative method for accurate tracking and tool registration with respect to spatially-registered intaoperative US volumes without relying on an external tracking device. This three-dimensional ultrasound (3DUS) will be integrated with a flexible, snake-like lightweight and inexpensive robotic, called the Active Cannula (AC), to facilitate precise placement of a steerable ultrasound thermal ablator into the liver and to monitor the progress of tissue ablation with real-time 3D registered ultrasound. Recent developments of implantable or interstitial high-power ultrasound applicators have demonstrated extremely controllable and penetrating heating patterns which can be shaped and dynamically altered, providing an ideal mechanism for conformable thermal surgery. This controllability and penetration is highly desirable and would provide significant improvement over existing RF and microwave (MW) technology used for minimally invasive thermal ablation of liver tumors. However, to date the extensive evaluation of this minimally invasive technology has been limited mostly to in vivo canine prostates and moderately perfused tissues, and have not included the design iterations and thorough evaluations necessary for treating tumors within highly perfused liver tissue. The preliminary thermal data from thermal therapy of perfused liver (Section C) are encouraging. Ultrasound Interstitial Thermal Therapy (USITT) technology is promising and we will extend the technology to optimize its use for the treatment of hepatic tumors. The overall goal of this research and development is to provide a true closed-loop system for steering, placement, guidance, percutaneous delivery of conformal ablative therapy, and on-line monitoring of treatment. PUBLIC HEALTH RELEVANCE: Hepatocellular carcinoma (HCC) is the most common type of common primary liver cancer and is associated with over one million cases diagnosed worldwide each year. In the United States specifically, HCC is being seen with increasing frequency, largely due to the incidence of known and clinically occult hepatitis C. Other primary malignancies are also on the rise in the U.S., including intrahepatic cholangiocarcinoma. Yet, metastatic disease from other sites to the liver is the most common hepatic malignancy overall in the U.S. Cancer of the colon and rectum account for the majority of these primary tumors which develop isolated liver metastases. While other primary tumors originating from gastrointestinal sites often develop hepatic metastases as well, tumors arising in other locations, including those of the breast and lung, also commonly develop hepatic metastases. For colorectal cancer specifically, approximately 20% of patients have clinically recognizable liver metastases at the time of their primary diagnosis. After resection of a primary colorectal cancer in the absence of apparent metastatic disease, approximately 50% of patients will subsequently manifest metastatic liver disease6. Given these figures, one can expect that at least 30,000 patients per year in the United States will develop metastatic colorectal cancer confined to the liver, each year. In selected patients, potentially curative therapies for primary and secondary liver cancer include surgical resection and in some cases liver transplantation. Unfortunately only a small percentage of patients are candidates for these treatments. Intraarterial approaches such as chemoembolization, while therapeutically useful in some cases, rarely achieves complete tumor destruction. For these reasons, an increasing interest has been focused on interstitial ablative approaches for the treatment of primary and metastatic liver cancer. Despite advances in the effectiveness of these therapies, precise targeting of the ablator device and monitoring of the zone of necrosis are still unsolved problems. The rationale for ablation therapy of liver tumors is evident. To begin, this approach often allows for greater preservation of uninvolved hepatic parenchyma, directing the treatment specifically to the tumor location. This feature is particularly beneficial for patients with hepatocellular carcinoma in the background of cirrhosis, where hepatic reserve is often limited. In cases of metastatic disease, tumors which are multiple, bilateral, centrally located, or in areas not technically resectable are potentially well suited for this approach. Additionally, localized ablative therapy may be applicable for some patients with isolated hepatic recurrence following liver resection, perhaps resulting in lower morbidity than repeat hepatic resection. Recent studies have demonstrated significant advantages of multi-transducer interstitial ultrasound applicators, most notably the capability to dynamically tailor the longitudinal and angular heating distribution which are important for conformable treatments and preserving critical non-targeted tissue. Recent studies have demonstrated significant advantages of multi-transducer interstitial ultrasound applicators, most notably the capability to dynamically tailor the longitudinal and angular heating distribution which are important for conformable treatments and preserving critical non-targeted tissue. Our goal is to develop a new system with integrated active cannula ultrasound ablator combination spatially- registered with 3D ultrasound image guidance that is widely affordable, including for community hospitals and satellite clinics. Furthermore, the proposed technology will be readily transferable to wide range of indications and usable with various ablative modalities. 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